PURPOSE:An inflammatory-immunological marker, neutrophil-to-lymphocyte ratio (NLR), was evaluated as a surrogate indicator for prognosis of advanced lung adenocarcinoma patients. METHODS:The subjects of this study were 199 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin as first-line therapy. The values of NLR were assessed at two time points: at baseline (pretreatment) and on day 1 of the second cycle (posttreatment). RESULTS:A higher posttreatment NLR was associated with a worse tumor response (median posttreatment NLR, 1.56 for partial response, 1.64 for stable disease, and 2.70 for progressive disease; P < 0.001). The risk of progression was higher when the posttreatment NLR was higher [hazard ratio (HR) = 1.23, 95 % confidence interval (CI) 1.15-1.31; P < 0.001]. A high posttreatment NLR was associated with an increased risk of death (HR = 1.13, 95 % CI 1.06-1.21; P < 0.001). These associations did not differ according to treatment arms. When total patients were divided into four groups according to the cutoff points of pre- and posttreatment NLRs, those with a high pretreatment NLR that declined substantially after treatment showed improved survival compared with those with a high pretreatment NLR that remained high even after treatment (median overall survival, 22.0 and 15.8 months, respectively; P < 0.001). CONCLUSIONS:A high posttreatment NLR is associated with poor prognosis. An early reduction in the NLR after effective treatment may indicate survival improvement in the patients with poor prognosis.

译文

目的:炎性免疫标记物,嗜中性粒细胞与淋巴细胞之比(NLR)被评估为晚期肺腺癌患者预后的替代指标。
方法:本研究的受试者为199位从不吸烟的晚期肺腺癌患者,他们参加了一项前瞻性随机III期研究(First-SIGNAL),比较吉非替尼与吉西他滨加顺铂作为一线治疗。在两个时间点评估NLR值:在基线(治疗前)和第二个周期的第1天(治疗后)。
结果:较高的治疗后NLR与较差的肿瘤反应相关(治疗后中位NLR为1.56,部分反应为1.64,稳定疾病为2.70,进行性疾病为2.70; P <0.001)。当治疗后的NLR较高时,进展风险较高[风险比(HR)= 1.23,95%置信区间(CI)1.15-1.31; P <0.001]。较高的治疗后NLR会增加死亡风险(HR = 1.13,95%CI 1.06-1.21; P <0.001)。这些关联根据治疗方式而没有不同。当根据治疗前和治疗后NLR的临界点将患者分为四组时,与治疗前NLR较高但仍在治疗后仍高的患者相比,治疗前NLR较高而在治疗后明显下降的患者的生存期得到了改善。总生存期分别为22.0和15.8个月; P <0.001)。
结论:较高的治疗后NLR与不良预后有关。有效治疗后NLR的早期降低可能表明预后不良患者的生存率得到了改善。

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